Despite improvements in the treatment of women with metastatic breast cancers (MBC), there are no curative treatment options. For the 20-25% of women with MBC who are HER2/neu (HER2) 3+, Herceptin(r) has become a mainstay of treatment in combination with chemotherapy. New approaches, however, are needed that will prolong progression-free survival (PFS) and overall survival (OS) for the 75-80% of the MBC patients who are HER2 0-2+ and are not eligible for Herceptin(r). In our previous phase I clinical trial, we have administered anti-CD3 activated T cells (ATC) "armed" with anti-CD3 x anti-HER2/neu bispecific antibody (HER2Bi) to women with both HER2-positive and HER2-negative MBC to determine their safety and the maximum tolerated dose. Arming ATC with HER2Bi makes every T cell into a HER2-specific cytotoxic T lymphocyte (CTL) with the potential to induce high levels of specific cytotoxicity that is independent of HER2 receptor-mediated mechanisms and thus, HER2 expression levels. Indeed, evaluation of immune responses in our phase I clinical trial patients suggests that infusions of Her2Bi-armed ATC induce robust immune responses regardless of the patient's HER2 status. Here, we propose a phase II trial that combines primary oncologist's choice of chemotherapy (ChemoT) consisting of 4 cycles or 4 months of followed by lymphodepletion with low dose fludarabine (Flu) and cyclophosphamide (Cy) before giving multiple infusions of Her2Bi-armed ATC to treat patients with MBC having HER2/neu 0, 1+, or 2+ amplification levels. The efficacy of the combined therapy for the entire group as measured by PFS (primary endpoint) will be compared to a median time to progression of 6 months derived from the literature for second line chemoT for MBC. We hypothesize that if Her2Bi-armed ATC infusions are capable of reversing the immunosuppressed-state of the patient, then infusions of Her2Bi-armed ATC after ChemoT will further enhance anti-tumor immunity directed at residual disease and improve progression free survival and tumor responses. Additionally, by lymphodepletion with Flu and Cy, we will provide an opportunity for the infused armed ATC to expand in vivo after infusion and thus, enhance MBC-specific immune-mediated cytotoxicity and/or to persist to develop central memory for tumor antigens. In Aim 2, we will also evaluate functional and phenotypic immunological changes in peripheral blood and/or at the tumor site. Aim 3 is designed to develop correlates between the systemic or tumor site immune responses monitored in Aim 2 and clinical outcomes in Aim 1. We predict that this approach involving Her2Bi-armed ATC-mediated anti-tumor "immunization" following second line chemotherapy for MBC will improve clinical outcomes.